title: Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland.
abstract: The melanocortin-2-receptor (MC2R)/MC2R accessory protein (MRAP) complex is critical to the production of glucocorticoids from the adrenal cortex. Inactivating mutations in either MC2R or MRAP result in the clinical condition familial glucocorticoid deficiency. The localisation of MC2R together with MRAP within the adrenal gland has not previously been reported. Furthermore, MRAP2, a paralogue of MRAP, has been shown in vitro to have a similar function to MRAP, facilitating MC2R trafficking and responsiveness to ACTH. Despite similar MC2R accessory functions, in vivo, patients with inactivating mutations of MRAP fail to be rescued by a functioning MRAP2 gene, suggesting differences in adrenal expression, localisation and/or function between the two MRAPs. In this study on the rat adrenal gland, we demonstrate that while MRAP and MC2R are highly expressed in the zona fasciculata, MRAP2 is expressed throughout the adrenal cortex in low quantities. In the developing adrenal gland, both MRAP and MRAP2 are equally well expressed. The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. Interestingly, expression of MC2R and MRAP in the undifferentiated zone would support the notion that ACTH may play an important role in adrenal cell differentiation and maintenance.
authors.affiliation: William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London EC1M 6BQ, UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Gorrigan
authors.forename: Leonardo
authors.initials: L
authors.lastname: Guasti
authors.forename: Peter
authors.initials: P
authors.lastname: King
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Clark
authors.forename: Li F
authors.initials: LF
authors.lastname: Chan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000302:Adrenal Cortex / Q000378:metabolism; D000307:Adrenal Gland Diseases / Q000235:genetics; D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D008156:Luciferases; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D015383:Zona Fasciculata / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005938:Glucocorticoids; C458099:MRAP protein, human; C551627:MRAP2 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D008156:Luciferases